MC-LR induces dysregulation of iron homeostasis by inhibiting hepcidin expression: A preliminary study. (December 2018)

• Record Type: Journal Article
• Authors: Wu, Jinxia; Yang, Lei; Zhang, Xiaofeng; Li, Yang; Wang, Jianyao; Zhang, Shenshen; Liu, Haohao; Huang, Hui; Wang, Yueqin; Yuan, Le; Cheng, Xuemin; Zhuang, Donggang; Zhang, Huizhen; Chen, Xinghai
• Is Part Of: Chemosphere. Volume 212(2018)
• Page Start: 572
• Page End: 584
• Publication Date: 2018-12
• Subjects: Microcystin-LR -- Hepcidin -- Iron homeostasis -- Hypoxia -- Hfe−/− mice; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2018.08.077
• Languages: English
• ISSNs: 0045-6535

Abstract

Abstract: The liver is an important iron storage site and a primary MC-LR target. C57BL/6 and Hfe −/− mice were used to investigate effects and mechanisms of MC-LR on systematic iron homeostasis. Body weight, tissue iron content, hematological and serological indexes, and histopathological were evaluated. Ultrastructure and iron metabolism-related genes and proteins were analyzed. MC-LR induced dose-dependent increases in red blood cells, hemoglobin, and hematocrit. In contrast MC-LR-induced dose-dependent decreases in mean corpuscular volume, hemoglobin, and hemoglobin concentration were observed both C57BL/6 and Hfe −/− mice. In both mouse species, serological indexes increased. Aggravated liver and spleen iron were observed in C57BL/6 mice, consistent with Perls' Prussian blue staining. However, an opposite trend was observed in Hfe −/− mice. C57BL/6 mice had lower Hamp1 ( Hepcidn ), Bmp6, Il-6, and Tmprss6 . Significant increased Hjv, Hif-1α and Hif-2α were observed in both C57BL/6 and Hfe −/− mice. MC-LR-induced pathological lesions were dose-dependent increase in C57BL/6 mice. More severe pathological injuries in MC-LR groups (25 μg/kg) were observed in Hfe −/− mice than in C57BL/6 mice. In Hfe −/− mice, upon exposure to 25 μg/kg MC-LR, mitochondrial membranes were damaged and mitochondrial counts increased with significant swelling. These results indicated that MC-LR can induce the accumulation of iron in C57BL/6 mice with the occurrence of anemia, similar to thalassemia. Moreover, dysregulation of iron homeostasis may be due to MC-LR-induced Hamp1 downregulation, possibly mediated by hypoxia or the IL6–STAT3 and BMP–SMAD signaling pathways. Highlights: MC-LR induced the accumulation of iron in C57BL/6 mice with the occurrence of anemia that similar to thalassemia. MC-LR reduced the expression of hepcidin that is the central hormone in regulating iron homeostasis in the body. The downregulation of hepcidin induced by MC-LR may be related to hypoxia, IL-6-STAT3, and BMP-SMAD signaling pathway and HIFs play important roles.